Liposomes can be used as templates to direct the formation of inorganic structures. Hentze et al. (2003) describe a procedure to form hollow silica particles of 60 to 120 nm diameter by first forming vesicles and addition of an inorganic precursor to silica to this vesicle dispersion. The vesicles act as templates for the directed growth of silica on their surface. In this way, hollow silica particles were formed with about a 2 nm-thick shell and with a core diameter identical to that of the template. Either discrete hollow particles or networks of linked or aggregated particles can be formed.
Liposomes and vesicles are further used to form multilamellar inorganic shells by first forming a multilamellar liposome or vesicle and then adding to the solution an inorganic precursor that does not hydrolyze rapidly in water, such as TEOS (tetraethyl orthosilicate). This precursor then accumulates between the lipophilic lipid layers, where it polymerizes and crosslinks to form a solid insoluble multilamellar inorganic multilamellar shell. The liposome or vesicles amphiphiles may be subsequently removed. For example, Tanevt and Pinnavaia (1998) described an approach to direct biomimetic assembly of lamellar silicas. The approach is based on the hydrolysis and condensation of a neutral silicon alkoxide precursor such as TEOS in the multilamellar regions of vesicle structure made from a neutral diamine bola-amphiphile. The bola-amphiphile acts as a neutral diamine template to form a framework for the precursor but also acts as a multilamellar vesicle-type nanoreactor governing the direction of framework growth and the particle architecture. In this approach, the multilamellar vesicle is first formed; then, an inorganic precursor that does not hydrolyze rapidly (e.g., TEOS) is added to the external solution, from which it diffuses into the spaces between the lamella and polymerizes therein.
Jung et al. (2000) disclosed the use of two different diazacrown-appended cholesterol gelators for solvent gelation. For example, one derivative was added to a solution containing aniline, water and TEOS and warmed and then cooled to form a gel. The gel formed contained linearly linked spherical meso- to micron-sized vesicles of 200 to 2000 nm diameter, wherein the linearly linked small vesicles caused the gelation. In effect, the spherical vesicle structures of organogels were formed into silica structures by the sol-gel polymerization of TEOS in the gel phase, wherein the spherical silica obtained in the acidic conditions consists of multilayered vesicle structure.
Kiatagiri et al., 2003, disclose a class of nano hybrid materials, called by the authors “Cerasome”, bearing a liposomal bilayer structure and surface, wherein by a sol-gel reaction a double chain proamphiphile having a trialkoxysilane as the head moiety self-assembles into a bilayer vesicle. The silica precursor then reacts to polymerize and crosslink resulting in vesicles comprised of silica shells. Other head group moieties can be used such that surface modification of the Cerasome with amino groups is achieved by replacing TEOS with 3-aminopropyl-triethoxysilane.
Amphiphiles have also been used to coat preformed inorganic particles. U.S. Pat. No. 5,441,746 discloses an electromagnetic wave-absorbing surface modified magnetic particles for use in medical applications. The magnetic particles are coated with an amphipathic organic compound and an amphipathic vesicle-forming lipid. These particles may be used in treatment of cancer and infectious diseases. In one approach, the wave absorbing magnetic core liposome is first coated with an amphipathic organic compound, which contains both a hydrophilic and hydrophobic moiety. For example, fatty acids, such as oleic acid, linoleic acid or linolenic acid, dispersed in an organic solvent, are directly added to the preformed particles. The coated particles are then dispersed in an organic solvent and then coated with a vesicle-forming lipid such as phosphatidylcholine, phosphatidic acid, phosphatidylinositol, phosphatidyl ethanolamine (PE), sphingomyelin and glyco-lipids, such as cerebroside and gangliosides. The coated particles comprise ferrite or mixed ferrite materials, preferably of a uniform, controllable size and narrow size distribution, wherein the primary component, the oxide, is of the formula M2(+3)M(+2)O4, wherein M(+3)  is Al, Cr or Fe, and M(+2)  is Fe, Ni, Co, Zn, Zr, Sr, Ca, Ba, Mg, Ga, Gd, Mn or Cd, and the oxides can be mixed with LiO, CdO, NiO, FeO, ZnO, NaO, KO and mixtures thereof. The targeted wave absorbing magnetic core liposome may be prepared to include ferrites useful as cancer chemotherapeutic agents. In one method of synthesis, the magnetic core liposomes are prepared to include PEG-PE and PG on the liposome backbone to aid in targeting to specific areas and to avoid reticuloendothelial system (RES) uptake.
In a similar approach, disclosed in U.S. Pat. No. 5,389,377, liposomes are provided containing a solid inorganic core consisting of metals and metal oxides of Fe, Co, Ni, Zn, Mn, Mg, Ca, Ba, Sr, Cd, Hg, Al, B, Sc, Ga, V, In, and mixtures thereof, coated with a first amphipathic organic compound and further coated with a second amphipathic vesicle forming lipid. The cores may be Fe3O4, Fe2O3, Al2O3, TiO2, ZnO, FeO, and Fe or mixtures thereof, the first amphipathic organic compound is preferably a fatty acid and the second amphipathic organic is preferably is a phospholipid or a glycolipid or mixtures thereof.
In US Patent Application 2002/0103517, nano-sized shells made from metals such as gold, silver, copper, platinum, palladium, lead, and iron, are housed within a liposome and the specific binding ligand is functionally incorporated into a liposome membrane. Gold is most preferred. Gold nano shells possess physical properties similar to gold colloid, in particular, a strong optical absorption due to the collective electronic response of the metal to light and are more amenable to a directed shift in their plasmon resonance and hence absorption or scattering wavelengths than the solid metal nanoparticles. The liposome will thus specifically bind to the receptor(s) of a target cell and deliver the contents to a cell. Such systems have been shown to be functional using systems in which, for example, epidermal growth factor (EGF) is used in the receptor-mediated delivery of a nucleic acid to cells that exhibit up regulation of the EGF receptor.
All the above approaches are based on first forming either the core nano-particle and then coating them with amphiphilic derivatives or first forming the liposome or vesicle and using them as a template to form an inorganic shell or the formation of a gel from the addition of amphiphiles to an organic solution, which forms structures inside the gel which are used to form inorganic particles.
In the use of amphiphiles to coat previously made particles, the role of the amphiphile is not to control or template the final inorganic particle, but rather to modify its existing surface properties. In all cases, the amphiphile and the inorganic precursor are not initially an intimate mixture in a common solvent. As a result, a given equilibrium for an equilibrium distribution of the solid inorganic precursor must occur. Thus, all these approaches for using templates of amphiphile aggregates and adding the precursors to the solutions containing the vesicles or liposomes, are difficult to control, the final product characteristics may require multiple steps, and the final product exhibits a certain lack of homogeneity. In addition, in the examples requiring the distribution of an inorganic precursor between the lamella of a vesicle or liposome, or in the procedure wherein the inorganic precursor is first in contact with water, then only compounds that undergo relatively slow reactions with water can be used as the compound must first form an equilibrium distribution within the amphiphilic structures before reacting to form a solid Thus, in many of the examples cited in the state of art, slow reacting tetraethyl orthosilicate (TEOS) is used and the use of faster reacting precursors such as titanum and zirconium alkoxides or similar derivatives cannot be used because of their rapid reactions within water.